Eisai Food and Chemical Co.

Chūō-ku, Japan

Eisai Food and Chemical Co.

Chūō-ku, Japan
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Kaneai N.,Shibaura Institute of Technology | Fukui K.,Shibaura Institute of Technology | Koike T.,Eisai Food and Chemical Co. | Urano S.,Shibaura Institute of Technology
Biological and Pharmaceutical Bulletin | Year: 2013

This study examines the ability of vitamin E to inhibit hyperoxia-induced loss of soluble N-ethylmaleimide- sensitive fusion protein attachment protein receptor (SNARE) proteins in the neuronal cytoplasm. Here, the effects of vitamin E on hyperoxia-induced changes in the expressions of N-ethylmaleimide-sensitive factor (NSF) and soluble NSF-attachment protein α (α-SNAP) in the rat brain were analyzed. When rats were subjected to hyperoxia, the expression of both SNARE proteins was markedly decreased compared to normal rats. Vitamin E significantly inhibited the decrease in the expression of NSF in rats subjected to hyperoxia. Rats showed the tendency to improve the loss of α-SNAP by vitamin E-supplementation, although it was not statistically significant. On the other hand, vitamin E deficient rats showed marked loss of these proteins in the brain in the absence of oxidative stress. These results suggest that hyperoxia induces a loss of SNARE proteins, which are involved in membrane docking between synaptic vesicles and pre-synaptic membranes, and that vitamin E prevents the oxidative damage of SNARE proteins. Consequently, it is implied that vitamin E inhibits impaired neurotransmission caused by oxidative stress through the prevention of oxidative damage to SNARE proteins by probably its antioxidant effect. © 2013 The Pharmaceutical Society of Japan.


Kaneai N.,Shibaura Institute of Technology | Sumitani K.,Shibaura Institute of Technology | Fukui K.,Shibaura Institute of Technology | Koike T.,Eisai Food and Chemical Co. | And 2 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2016

To define whether tocotrienol (T-3) improves cognitive deficit during aging, effect of T-3 on learning and memory functions of aged rats was assessed. It was found that T-3 markedly counteracts the decline in learning and memory function in aged rats. Quantitative analysis of T-3 content in the rat brain showed that the aged rats fed T-3 mixture-supplemented diet revealed the transport of α- and γ-T-3 to the brain. In contrast, normal young rats fed the same diet did not exhibit brain localization. Furthermore, the T-3 inhibited age-related decreases in the expression of certain blood brain barrier (BBB) proteins, including caludin-5, occludin and junctional adhesion molecule (JAM). It was found that the activation of the cellular proto-oncogene c-Src and extracellular signal-regulated protein kinase (ERK), in the mitogen-activated protein kinase (MAPK) cell signaling pathway for neuronal cell death, was markedly inhibited by T-3. These results may reveal that aging induces partial BBB disruption caused by oxidative stress, thereby enabling the transport of T-3 through the BBB to the central nervous system, whereupon neuronal protection may be mediated by inhibition of c-Src and/or ERK activation, resulting in an improvement in age-related cognitive deficits. ©2016 JCBN.


Takeda R.,Kinki University | Koike T.,Eisai Food and Chemical Co. | Taniguchi I.,Eisai Food and Chemical Co. | Tanaka K.,Kei Medical Clinic
Phytomedicine | Year: 2013

Hydroxytyrosol is mainly found in olive leaves after hydrolysis of oleuropein and has anti-oxidant, anti-bacterial, and anti-inflammatory properties. The aim of this study was to investigate the effect of hydroxytyrosol for alleviating the pain in patients with gonarthrosis. We conducted a double-blind clinical trial in which hydroxytyrosol or placebo was administered to adult patients with gonarthrosis for 4 weeks. The group administered hydroxytyrosol showed significant improvement in the Japanese Orthopedic Association score (pain measurement index) and the visual analog scale score compared to the placebo group. © 2013 Elsevier GmbH.


Gong D.,Dalian Medical University | Geng C.,Dalian Medical University | Jiang L.,Dalian Medical University | Wang L.,Dalian Medical University | And 2 more authors.
Journal of Medicinal Food | Year: 2011

We investigated the restorative effect of orally administered olive leaf extract (OLE) on experimentally produced cartilaginous injuries in rabbits. In total, three holes in the left stifle joint, including one in the medial trochlear ridge and two in the trochlear sulcus (proximal and distal) of articular cartilage, were prepared surgically using a drill. For the control group only tap water alone was administered daily, and for the OLE group a water-based solution of OLE (500 mg/kg/day) was administered daily. The injured areas were observed macroscopically and histologically at 3 weeks after the operation. The results indicate that OLE facilitated healing of the three holes and increased the weight of the biceps femoris muscle. Histological examination revealed that in the OLE group, matured cartilage tissues and connective tissues were mixed with regenerated or maturing cartilage tissues with massive proliferation in the injured parts, around which the proliferation of undifferentiated blast cells and the tissue with cartilage substrates were observed. The histological score of the OLE group was significantly lower than that of the control group. The percentage of proliferating cell nuclear antigen+positive cartilage cells in the OLE group was higher than in the control group. Mean density of the restored area observed with Safranin O staining was higher in the OLE group than in the control group. Therefore, OLE is effective for enhancing the healing of cartilaginous injuries. OLE may also have a beneficial effect of slowing and reducing the pathogenesis of degenerative joint diseases in humans. Copyright 2011, Mary Ann Liebert, Inc.


Nakaso K.,Tottori University | Horikoshi Y.,Tottori University | Takahashi T.,Tottori University | Hanaki T.,Tottori University | And 4 more authors.
Neuroscience Letters | Year: 2016

Neuroprotection following signal transduction has been investigated recently as a strategy for Parkinson's disease (PD) therapy. While oxidative stress is important in the pathogenesis of PD, neuroprotection using antioxidants such as α-tocopherol have not been successful. δ-tocotrienol (δT3), a member of the vitamin E family, has received attention because of activities other than its antioxidative effects. In the present study, we examined the estrogen receptor-β (ERβ)-mediated neuroprotective effects of δT3 in a mouse model of PD. ERβ is expressed in neuronal cells, including dopaminergic neurons in the substantia nigra. Daily forced oral administration of δT3 inhibited the loss of dopaminergic neurons in the substantia nigra. In addition, the ER inhibitor tamoxifen canceled the neuroprotective effects of δT3. Moreover, δT3 administration improved the performance of the PD mice in the wheel running activity, while tamoxifen inhibited this improved performance. These results suggest that the oral administration of δT3 may be useful in the treatment of PD patients, and ERβ may be a candidate target for the neuroprotection activity of δT3. © 2015 Elsevier Ireland Ltd.


Ouchi A.,Ehime University | Nagaoka S.-I.,Ehime University | Suzuki T.,Eisai Company | Izumisawa K.,Eisai Company | And 2 more authors.
Journal of Agricultural and Food Chemistry | Year: 2014

Measurements of aroxyl radical (ArO•)-scavenging rate constants (ks AOH) of antioxidants (AOHs) [α-, β-, γ-, and δ-tocopherols (TocHs) and -tocotrienols (Toc-3Hs)] were performed in ethanol solution via stopped-flow spectrophotometry. k s AOH values of α-, β-, γ-, and δ-Toc-3Hs showed good agreement with those of the corresponding α-, β-, γ-, and δ- TocHs. ks AOH values were measured not only for each antioxidant but also for mixtures of two antioxidants: (i) α-TocH with β-, γ-, or δ-TocH and (ii) α-TocH with α-, β-, γ-, or δ-Toc-3H. A synergistic effect in which the ks AOH value increases by 12% for γ-TocH (or by 12% for γ-Toc-3H) was observed for solutions including α-TocH and γ-TocH (or γ-Toc-3H). On the other hand, a cancel effect in which the ks AOH value decreases (a) by 7% for β-TocH (or 11% for β-Toc-3H) and (b) by 24% for δ-TocH (or 25% for δ-Toc-3H) was observed for solutions including two kinds of antioxidants. However, only a synergistic effect may function in edible oils, because contents of β- and δ-TocHs (and β- and δ-Toc-3Hs) are much less than those of α- and γ-TocHs (and α- and γ-Toc-3Hs) in many edible oils. UV-vis absorption of α-Toc •, which was produced by reaction of α-TocH with ArO •, decreased remarkably for coexistence of α-TocH with β-, γ-, or δ-TocH (or β-, γ-, or δ-Toc-3H), indicating that the prooxidant effect of α-Toc• is suppressed by the coexistence of other TocHs and Toc-3Hs. © 2014 American Chemical Society.


Muto C.,Kanagawa Institute of Technology | Yachi R.,Kanagawa Institute of Technology | Aoki Y.,Eisai Food and Chemical Co. | Koike T.,Eisai Food and Chemical Co. | And 2 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2013

The present study was carried out to investigate the effect of vitamin E analogs, especially gamma-tocotrienol (γ-T3), on hepatic TG accumulation and enzymes related to fatty acid metabolism in three types of rat primary hepatocytes: (1) normal hepatocytes, (2) hepatocytes incubated in the presence of palmitic acid (PA), and (3) hepatocytes with fat accumulation. Our results showed that γ-T3 significantly reduced the TG content of normal hepatocytes. γ-T3 also increased the expression of carnitine palmitoyltransferase 1 (CPT1A) mRNA, and tended to reduce that of sterol regulatory element binding protein 1c (SREBP-1c) mRNA. In addition, γ-T3 markedly suppressed the gene expression of both C/EBP homologous protein (CHOP) and SREBP-1c induced by PA. As these two genes are located downstream of endoplasmic reticulum (ER) stress, their suppression by γ-T3 might result from a decrease of ER stress. Moreover, γ-T3 suppressed the expression of interleukin 1β (IL-1β), which lies downstream of CHOP signaling. Taken together, our data suggest that γ-T3 might prevent hepatic steatosis and ameliorate ER stress and subsequent inflammation in the liver. ©2013 JCBN.


Yachi R.,Kanagawa Institute of Technology | Yachi R.,University of Tokyo | Muto C.,Kanagawa Institute of Technology | Ohtaka N.,Kanagawa Institute of Technology | And 4 more authors.
Journal of Clinical Biochemistry and Nutrition | Year: 2013

It has been reported that α-tocopherol (α-Toc), a vitamin E analog, is effective for treatment of non-alcoholic steatohepatitis (NASH). However, it is unknown whether or not other vitamin E analogs are effective. Therefore we designed a new rat model of steatohepatitis induced by tumor necrosis factor-α (TNF-α) stimulation, and used it to investigate the effects of vitamin E analogs. The rat liver triglyceride content increased with the dosage of TNF-α/D-galactosamine (GaIN), but was suppressed by intake of both toco-trienol (T3) and α-tocopherol. Moreover, lipid peroxides (thiobar-bituric acid-reactive substances) level in the liver level was also lower in both groups after tocotrienol and α-Toc intake. Intake of both tocotrienol and α-tocopherol also tended to control the increase of liver damage marker activity. In the tocotrienol and α-tocopherol groups, increases of inflammatory cytokines mRNA expression in the liver were inhibited, and these effects were considered to contribute to improvement of inflammation and fibrosis. The expression of mRNAs for inflammatory cytokines in rat primary hepatocytes was increased by TNF-α stimulation, but was inhibited by addition of α-Tocotrienol and γ-tocotrienol. Transforming growth factor-β1 mRNA expression in particular was significantly inhibited by γ-tocotrienol. These findings suggest that tocotrienol species are effective for amelioration of steatohepatitis, and that tocotrienol and α-tocopherol exert a synergistic effect. © 2013 JCBN.


Umeno A.,Japan National Institute of Advanced Industrial Science and Technology | Takashima M.,Japan National Institute of Advanced Industrial Science and Technology | Murotomi K.,Japan National Institute of Advanced Industrial Science and Technology | Nakajima Y.,Japan National Institute of Advanced Industrial Science and Technology | And 3 more authors.
Journal of Oleo Science | Year: 2015

Olive leaf has great potential as a natural antioxidant, and one of its major phenolic components is oleuropein. In this study, the antioxidant activity of oleuropein against oxygen-centered radicals was measured by examining its sparing effects on the peroxyl radical-induced decay of fluorescein and pyrogallol red, in comparison with related compounds. The antioxidant capacity of oleuropein against lipid peroxidation was also assessed through its effect on the free radical-induced oxidation of methyl linoleate in a micelle system. On a molar basis, oleuropein and hydroxytyrosol inhibited the decay of fluorescein for longer than both homovanillic alcohol and the vitamin-E mimic 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (Trolox), but did not suppress pyrogallol red decay in a concentration-dependent manner. Measurement of the fluorescein decay period revealed that the stoichiometric number of oleuropein and hydroxytyrosol against peroxyl radicals was twice that of Trolox, which is substantially higher than expectations based on chemical structure. Oleuropein and hydroxytyrosol were also more effective than Trolox and homovanillic alcohol at suppressing the oxidation of methyl linoleate in the micelle system. Thus, both oleuropein and hydroxytyrosol exhibit high antioxidative activity against lipid peroxidation induced by oxygen-centered radicals, but the high reactivity of phenolic/catecholic radicals makes their mechanism of action complex. © 2015 by Japan Oil Chemists’ Society.

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